Fruit fly yields clue to biological clock

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In the latest issue of Science, Howard Hughes Medical Institute (HHMI) investigator Amita Sehgal and colleagues at the University of Pennsylvania School of Medicine

subjected fruit flies to pulses of light then examined the biochemical consequences, showing how light causes cells to break down a key biological clock protein called 'timeless' (TIM).

"If we understood exactly which component needed to be regulated to reset the biological clock, we could target just that component with drugs," said Sehgal "Such drugs might aid treatment of jet lag and seasonal depression caused by absence of light in winter".

Biological, or circadian, clocks operate on a roughly 24-hour cycle that governs such functions as sleeping and waking, rest and activity.

Light itself doesn't directly reset the clock. Rather, light strikes photoreceptors in a fly's body, which then send signals to the clock. These signals somehow reduce levels of TIM. When the level of TIM reaches a low point, the timeless gene, TIM, is switched on to replenish TIM's levels and reset the biological clock.

Sehgal hypothesized that cell structures called proteasomes, large agglomerations of enzymes, played a key role in degrading TIM. Proteasomes break down unneeded proteins.

To test whether proteasomes degraded the TIM protein, Sehgal and her colleagues pulsed flies with light and found that TIM was indeed degraded in extracts prepared from cells. The researchers then demonstrated that they could use chemicals that inhibit proteasome enzymes to block TIM breakdown.